PALOMA-2 Results for First-Line Subcutaneous Amivantamab in NSCLC

In an interview with Targeted Oncology, Sun Min Lim, MD, PhD, Yonsei University Cancer Center, discusses results from cohort 2 of the PALOMA-2 study (NCT05498428), which evaluated a subcutaneous (SC) formulation of amivantamab (Rybrevant) combined with chemotherapy as a first-line treatment for patients with advanced non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (ex20ins) mutations. The results demonstrate that the SC regimen offers efficacy consistent with the previously established intravenous (IV) formulation, alongside a significantly improved safety profile and greater convenience.

The study met its primary end point, showing a high overall response rate (ORR) of 76% as assessed by investigators. This, along with a median progression-free survival (PFS) of 12.2 months and a median duration of response of 10.6 months, is consistent with the pivotal PAPILLON study (NCT04538664) of the IV formulation.

Crucially, the SC formulation demonstrates superior tolerability. The rate of administration-related reactions (ARRs) was reduced 7-fold, occurring in only 6% of patients compared with 42% with the IV formulation in PAPILLON. Pharmacokinetic (PK) data further confirmed that the SC regimen achieves consistent plasma concentrations. These findings strongly support the conclusion that subcutaneous amivantamab plus chemotherapy represents a new standard of care, offering comparable efficacy with added tolerability and convenience benefits for this patient population.

IV amivantamab combined with chemotherapy is an approved first-line treatment for advanced NSCLC with EGFR ex20ins mutations. This approval was based on the PAPILLON study where the combination significantly prolonged median PFS compared with chemotherapy alone (11.4 months vs 6.7 months) and achieved a blinded independent central review-assessed ORR 73%.

While effective, the IV formulation is associated with infusion-related reactions. A SC formulation was developed to improve tolerability and patient convenience. The PALOMA-3 study (NCT05388669) previously established noninferior PK and ORR for amivantamab SC compared with IV, along with fewer ARRs and a much shorter administration time (< 5 minutes). This led to its approval by the European Commission.

REFERENCE:

Lim SM, Tan JL, Wang J, et al. First-Line Subcutaneous Amivantamab Plus Chemotherapy in EGFR Exon 20 Insertion-Mutated Advanced NSCLC: Results from PALOMA-2. Presented at: IASLC 2025 World Conference on Lung Cancer; September 5–9, 2025; Barcelona, Spain.